computational systems biology

Computational Systems Biology

Lecture 2: Enzymes

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Images from: David L. Nelson, Lehninger Principles of Biochemistry, IV Edition, Freeman ed. or under creative commons license (search for images at http://search.creativecommons.org/)

W. http://bcs. for general reference) – Lehninger Chapter 6 – Enzymes (pp 190-200.com/lehninger/ • Enzymes – Lehninger Chapter 1. for general reference) (page numbers refer to the 4th edition) 2 .whfreeman. Freeman ed. peptides and proteins (pp 75-89.computational systems biology Suggested reading Book: David L. H.Principles of Biochemistry. 4th Edition (or 3rd Edition). Nelson.3 – Enzymes promote sequences of chemical reactions (pp 26-27) – Lehninger Chapter 3 – Amino acids. Lehninger .

computational systems biology Summary • What is an enzyme • Enzymes 3D structures • How enzyme work: enzymatic catalysis • The Enzyme Classification (EC) codes 3 .

g. actin in the muscles). the protein is often called oligopeptide/polypeptide or simply peptide) • • Thousands of different proteins are built with the same ubiquitous set of 20 amino acids (the protein “alphabet”) Some proteins have structural roles (e. other have catalytic (chemical-reaction-making) activity and are called enzymes A polypeptide with 4 amino acids (Ala-Glu-GlyLys) The electrically charged groups are shown in red In a longer protein the electrically charged lateral groups can line a pocket of the enzyme 3D structure to generate an active reaction site (see following slides) • • • 4 .computational systems biology Enzymes are proteins • In general. a protein is a chain of amino acids (aa) covalently linked (when the chain is short ~5-10 aa.

computational systems biology 20 amino acids The 1 letter and 3 letters codes 5 .

computational systems biology Proteins come in all shapes and sizes 6 .

IV Edition. H. . Nelson. Lehninger Principles of Biochemistry. Freeman ed.computational systems biology Enzymes 3D structure • Enzymes are proteins and their activities depends on the 3D structure of the amino acids that compose them (note: also some RNAs have catalytic activity but they won’t be covered in this course) 7 Images from: David L. W.

computational systems biology PDB .do • How is the data collected? Every 3D protein sequence has to be deposited in PDB before publication in reviewed journals 8 .Database of protein structures • PDB (RCSB Protein Data Bank) • http://www.rcsb.org/pdb/home/home.

computational systems biology Secondary structure • Common secondary structures are alpha helixes (here in different graphical representations) • And beta sheets 9 .

computational systems biology Structural domains • Recurring motifs (here the beta-alpha-beta loop) are the basis for protein structural classification • Enzymes with similar sequences and structural domains / motifs are classified in the same protein family 10 .

computational systems biology Interpro: the protein families database • InterPro is a database of protein families. domains and functional sites Identifiable features found in known proteins can also be scanned against unknown protein sequences (here an example of domain common to enzymes that use iron as cofactor to cut an hydrogen atom from an alcool). • • InterPro incorporates data from other databases 11 .

computational systems biology How enzymes work • IMPORTANT: enzymes do NOT and cannot affect the equilibrium / free energy difference of a reaction • Enzymes enhance the reaction rates (molecules produced per second) by lowering the activation energy of the transition state ΔG‡cat 12 .

H. Freeman ed. IV Edition.computational systems biology Images from: David L. W. Transition state energy changed by an enzyme (in blue) 13 . Lehninger Principles of Biochemistry. Nelson.

H.computational systems biology The enzyme action on the transition state 14 Images from: David L. Nelson. Lehninger Principles of Biochemistry. IV Edition. Freeman ed. W. .

W. . the active site appears painted in red From: David L. Lehninger Principles of 15 Biochemistry.computational systems biology The enzyme active site The red molecule is the substrate. Nelson. IV Edition. H. Freeman ed.

W. H. .com/lehninger/ clicking on  Chapter 6: Enzymes  16mechanism animation  fig 6. Freeman ed. IV Edition. Lehninger Principles of Biochemistry.whfreeman. Nelson.computational systems biology Enzyme: The surface inside the active site You can see a flash demo of this enzymatic reaction on: http://bcs.21 mechanism for chymotrypsin Images from: David L.

computational systems biology E.Oxidoreductases EC 2 .Transferases EC 3 . Enzyme nomenclature • • Enzymes are named depending on the reaction they catalyse.Hydrolases EC 4 .Ligases 17 .C.Lyases EC 5 .Isomerases EC 6 . Examples of enzyme groups are: • • • • • • EC 1 .

4 phosphatidate phosphatase EC 3.3 Phosphoric Monoester Hydrolases – – – – – – – – – – 18 EC 3.1.computational systems biology An example of E.1.7 3'(2').1.1. enzyme nomenclature EC 3.10 glucose-1-phosphatase – EC 3.1.6 3'-nucleotidase EC 3.3.3.3.1.3.1.11 fructose-bisphosphatase .3 phosphoserine phosphatase EC 3.1.1.5'-bisphosphate nucleotidase EC 3.C.3.1 Hydrolases Acting on Ester Bonds • EC 3.3.3.3.9 glucose-6-phosphatase EC 3.1 alkaline phosphatase EC 3.5 5'-nucleotidase EC 3.8 3-phytase EC 3.3.3.1.1.1.3.2 acid phosphatase EC 3. Hydrolases  EC 3.

qmul.chem.html The reaction involves the hydrolysis (separation) of a phosphate group here represented by Pi The “P” representing the phosphate group that appears on the top region of the D-fructose-1.uk/iubmb/enzyme/reaction/polys acc/Calvin2.ht ml The site also contains the reaction diagram shown here: http://www.ac.qmul.11 From the IUBMB (International Union of Biochemistry and Molecular Biology) web site: http://www.uk/iubmb/enzyme/ one can reach a record for the enzyme: EC 3.computational systems biology Example: fructose-bisphosphatase EC 3.chem.chem. 19 .3.qmul.1.ac.1.ac.11 (fructose-bisphosphatase): http://www.6-biphosphate substrate molecule has disappeared after the reaction.uk/iubmb/enzyme/EC3/1/3/11.3. and the product is now called Dfructose 6-phospate (the phosphate group in position 1 is no more there).

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